Case of the Week: An Intentional Overdose

Author: Dan Suarez 

Reviewer: Sarah Berg  


You are working a night shift in the behavioral health pod when EMS arrives with a new patient. EMS states that they were called by the patient’s friend after patient disclosed that he attempted to overdose on his psychiatric medications. He took 12 tabs of Lithium and a couple Ablify.  

 

Vitals: BP 122/90, HR 74, RR 17, T 36.1, O2 99% RA 

 

What questions do you want to ask this patient during your interview? 

              (specific to this patient)  

  • What is the dose and formulation of your Lithium and aripiprazole (Abilify)?  

  • What time did you take these medications? Did you take them all at once or was the ingestion spaced out over time? What was the route of ingestion?  

  • How long have you been taking Lithium? 

 

(general to all patients who present with overdose) 

  • What symptoms are you having?  

  • Any co-ingestants (APAP, ASA, alcohol, drugs)?  

  • Are you still having thoughts of wanting to harm yourself/others?  

  • Audio/visual hallucinations? Have you ever tried to overdose in the past? Have you ever been psychiatrically hospitalized?  

 

Charlie is an 18 yo male who recently started college at a local university. He is feeling overwhelmed in class and distraught about being so far from his family and home. 2 hours ago, he took 12 tablets of his extended-release Lithium (he does not know the dosage) in an attempt to kill himself. He also took “3 or 4” Abilify. He told his roommate who then called PD. He has developed a fine tremor in his hands, but denies any other symptoms. Denies co-ingestions and other forms of self-harm. He no longer wishes to die and is remorseful of his actions. He has been on Lithium for the last 4 years at a stable dose.  

 

What are you going to look for on your physical exam? 

  • Neuro 

    • Initially fine tremor (can occur with therapeutic use, will worsen with intoxication)1 

    • Ataxia, dysarthria, choreiform movements, coarse tremor, fasciculation, myoclonus, nystagmus, hyperreflexia  

  • GI: n/v, diarrhea 

  • CV: ECG with QTc prolongation, Brugada phenocopy, pseudoinfarction pattern. Can have hypotension and bradycardia  

  • Thorough skin exam for signs of self-harm  

 

Charlie’s physical exam:            

  • BP 122/90, HR 74, RR 17, T 36.1, O2 99% RA 

  • ECG with normal intervals, normal conduction 

  • BL hands with fine tremor (which Charlie states is worse than normal) 

  • Normal bowel sounds. Remainder of PE wnl.  

 

What are your next steps regarding labs, interventions, phone calls? 

  • In addition to your normal psych/tox labs (CBC, CMP, TSH, UDS, ETOH, ECG) you should send a Lithium level, as well as acetaminophen and salicylate levels to confirm the narrative 

  • Charlie is an otherwise healthy individual. Treatments for Li overdose include hyperhydration and dialysis, so it would be a good idea to start some fluids while you’re figuring out the magnitude of this ingestion.  

  • You should call toxicology. The timing of this phone call depends on the clinical picture. You know that treatment (discussed below) is decided based on symptoms and lithium level. Charlie looks very stable and his only symptom is mild tremor, but you decide to call tox early, given that these cases can be difficult to manage.  

    • Our tox department has explicitly stated that they prefer to be contacted early in these cases 

  • You should call psychiatry as well, once the patient is medically cleared. You may consider getting psychiatry involved earlier if the patient’s mental status is conducive to a psychiatric interview, but be cognizant to prioritize medical and toxicological evaluation and intervention.   

  • Calling collateral (in this instance, patient’s girlfriend, friends or family if you are able to reach them) can provide important context and additional information  

 

 

Shortly after, Charlie’s lithium level returns at 1.3 mmol/L (upper limit of normal is 1.2). You call toxicology to discuss the case. They help you confirm that the patient is on 450 mg extended release lithium. This initial level was drawn 3h after ingestion.  They recommend sending a level at 6h post-ingestion, which returns at 2.2 mmol/L. Based on the increasing trend at 6h, tox recommends hyperhydration with LR at 200ml/hr (following initial bolus of 2L) and whole bowel irrigation (polyethylene glycon via NG tube at 2L/hr until clear rectal effluent).   

 

Charlie is admitted for 2 days, during which time his Li level trends back to normal range. He is cleared by the tox and psych services for discharge home and encouraged to follow up with his established psychiatric care. He was restarted on all home meds, including lithium prior to discharge.   

 

 

 

Discussion:  

 

  • Background:  

    • Lithium is one of the most effective agents used to treat bipolar disorder. Its mechanism(s?) of action is complex and not completely understood. It has a problematically narrow therapeutic index.  

    • Tissue distribution of Lithium and time to steady state can be prolonged. This phenomenon is extremely important to the interpretation of Lithium levels. If Lithium level is checked within 1-4 hours after taking Lithium, the level will not reflect the steady state concentration (expect a higher plasma level after taking Lithium. May be falsely interpreted as being elevated).  

    • Immediate release lithium is absorbed within 1-2 hours, and extended-release formulations within 4-6 hours. Distribution of lithium to the brain is relatively slow and takes up to 24 hours.  

    • Clinical signs and symptoms seem to be a more valuable indicator of brain Lithium concentration than serum measurements. 

    • Lithium is primarily excreted by the kidneys. Lithium and sodium are neighbors on the periodic table and are both reabsorbed largely in the proximal tubule. Renal stimulation to retain sodium (volume depletion) will trigger the reabsorption of lithium as well. Conversely, anything prompting the renal secretion of sodium (IV fluid) will prompt the renal excretion of sodium and Li together.

Types of lithium toxicity:  

  • Acute 

    • Nausea, vomiting, diarrhea 

    • Orthostatic hypotension 

    • Large overdoses may absorb more slowly – prolonged symptoms 

  • Chronic  

    • Patient has a steady concentration of lithium, then something upsets the lithium homeostasis (i.e. renal injury, salt depletion, another pharmacologic agent effects resorption or excretion) 

    • Tremor may be present even in therapeutic levels 

    • Fasciculations, hyperreflexia, clonus, dysarthria, nystagmus, ataxia 

    • Confusion à coma. Seizures.  

  • Acute on chronic 

    • GI and neurologic effects 

    • Difficult to interpret levels 

  • Workup 

    • ALWAYS consider checking lithium levels on any patient who takes lithium in your ED, but certainly if you suspect Li intoxication  

    • If acute-on-chronic ingestion is suspected, check levels q2-4h until they peak (if extended release, may not peak for >24h) 

  • Treatment 

    • Initial treatment of toxicity should be hyperhydration (1.5-2x maintenance, reasonable to start with 200 mL/hr in an adult). Continue hyperhydration until concentration is <1 mmol/L. 

    • The Lithium nomogram below can be used to predict whether concentration will be >1 mmol/L at 36 hours. Can be used to determine the utility of dialysis (Buckley et al.) 

Extrip recommends ECTR (extracorporeal treatment, AKA dialysis) in patients with severe Li poisoning (level 1D recommendation)  

  • Indications for ECTR include if renal function is impaired and Li level > 4.0 mEq/L, or if there is presence of decreased LOC, seizures, dysrhythmias   

  • The decision to dialyze is difficult, and there are a few studies that show no difference in patients who were dialyzed vs not dialyzed.  

  • Avoid meds which impair renal function and will impair Li excretion (NSAIDs, ACE-i) 

  • Li is a positive ion, thus is not absorbed by activated charcoal 

  • Whole bowel irrigation (polyethylene glycol) may be considered following large ingestion of sustained release tablets to prevent ongoing absorption and toxicity  

Outcomes 

  • Mortality is low (roughly 1%) 

  • SILENT (Syndrome of Irreversible Lithium-Effectuated NeuroToxicity)  

    • Potentially permanent neuro injury from Li toxicity, mechanism is unclear. Very rare, discussed mostly in case reports and continues to be debated by experts 

    • Thought to occur more commonly in cases with chronic intoxication than acute toxicity 

    • Evidence does not support that dialysis prevents SILENT syndrome L  

    • Confusingly, rapid reduction in Li levels may correlate with increased risk of SILENT syndrome, possibly related to osmotic shifts and rapid withdrawal from Li.  


References  

  1. Farkas J. Lithium intoxication - EMCrit Project. EMCrit Project. https://emcrit.org/ibcc/lithium/. Published February 12, 2023.

  2.  Hedya SA, Avula A, Swoboda HD. Lithium Toxicity. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499992/ 

  3. Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol. 2015;10(5):875-887. doi:10.2215/CJN.10021014

  4. Buckley NA, Cheng S, Isoardi K, Chiew AL, Siu W, Vecellio E, Chan BS. Haemodialysis for lithium poisoning: Translating EXTRIP recommendations into practical guidelines. Br J Clin Pharmacol. 2020 May;86(5):999-1006. doi: 10.1111/bcp.14212. Epub 2020 Feb 11. PMID: 31912536; PMCID: PMC7163377. 

  5. Long N. Lithium toxicity. Life in the Fast Lane • LITFL. https://litfl.com/lithium-toxicity/. Published November 3, 2020. 

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